Reduction of postchallenge hyperglycaemia prevents acute endothelial dysfunction in subjects with impaired glucose tolerance

OBJECTIVES: To investigate whether selective reduction of postchallenge hyperglycaemia influences acute endothelial dysfunction, a very early manifestation of vascular disease, in patients with impaired glucose tolerance. METHODS: In a randomized, double-blind, placebo-controlled, cross-over study the acute effect of 200-mg acarbose was investigated in 28 subjects with diagnosed impaired glucose tolerance. Flow-mediated dilation (FMD) of the brachial artery was determined as a measure of endothelial function before and 2 and 3 h after ingestion of 100-g saccharose. Asymmetrical dimethylarginine (ADMA) was measured by high-performance liquid chromatography. RESULTS: A negative correlation was observed between the changes of glucose and FMD (r = 0.416, P = 0.0018) 2 h after ingestion of saccharose. At 3 h, neither blood glucose nor FMD were different from baseline. Changes of both blood glucose (P = 0.0007) and FMD (P = 0.046) were significantly lower after administration of acarbose. Subgroup analysis revealed that the effect of acarbose was restricted to those subjects with an increase of blood glucose above the median increase of glycaemia. No changes of plasma ADMA were observed. CONCLUSIONS: Our data clearly demonstrate that the postchallenge alteration of vascular function in patients with impaired glucose tolerance is caused by the acute elevation of glycaemia but not mediated by ADMA.